Fig. 5. Proposed summary of the relationship between the gut microbiome and the blood-brain barrier.

A (i) Factors such as the environment, age, circadian rhythm, medication/drugs, exercise, infection, diet and stress can affect the composition and landscape of the gut microbiota. (ii) the gut microbiota and colonized bacteria produce metabolites. These metabolites produced alter with regards to relative concentrations and molecules with changes in microbiota. (iii) gut-derived microbial metabolites cross the gut lumen whether as direct molecules or in derived forms and enter circulation. (iv) once in circulation, the microbial-derived metabolites can interact with the BBB. B In the absence of a gut microbiota (germ-free animals) or where there are compositional alterations in the gut microbiota, microbial metabolites are not produced or are differentially produced that can enter systemic circulation and the lack or increase in microbial-derived metabolites is associated with BBB dysfunction.